Association of [3H]nipecotic acid binding with the high-affinity γ-aminobutyric acid uptake system in human brain

A new potent, blood–brain barrier permeable γ-aminobutyric acid (GABA) uptake blocker, 1-[2-[bis[4-(trifluoromethyl)-phenyl]methoxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid (CI-966) was administered systemically by i.p. injection (5 mg/kg) in Sprague–Dawley rats under urethane anaesthesia. Twenty to thirty minutes after injection there was a highly variable, but overall significant, enhancement of the inhibition of hippocampal population spikes by GABA applied by microiontophoresis in the CA1 region. Like the effect of nipecotic acid (applied locally by iontophoresis), the potentiation by CI-966 was clearest when GABA was applied in or near the stratum pyramidale where its action normally is weakest and shows the most pronounced fading. This change in GABA potency is most simply explained by a reduction in GABA uptake.Key words: GABA, muscimol, nipecotic acid, GABA-uptake blocker, epilepsy.

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High-Affinity, Sodium-Dependent ?-Aminobutyric Acid Uptake by Slices of Rat Ovary

Journal of Neurochemistry ◽

10.1111/j.1471-4159.1983.tb11322.x ◽

1983 ◽

Vol 40 (2) ◽

pp. 582-584 ◽

Cited By ~ 15

Author(s):

Sándor L. Erdó

Keyword(s):

Aminobutyric Acid ◽

Acid Uptake ◽

High Affinity ◽

Sodium Dependent ◽

Rat Ovary

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Structure–activity studies on the inhibition of γ-aminobutyric acid uptake in brain slices by compounds related to nipecotic acid

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y79-089 ◽

1979 ◽

Vol 57 (6) ◽

pp. 581-585 ◽

Cited By ~ 17

Author(s):

J. D. Wood ◽

D. Tsui ◽

J. W. Phillis

Keyword(s):

Cortical Neurons ◽

Therapeutic Potential ◽

Brain Slices ◽

Aminobutyric Acid ◽

Gaba Uptake ◽

Acid Uptake ◽

Nipecotic Acid ◽

Depressant Action ◽

Methyl Derivatives ◽

Derivatives Of

Various N-methyl derivatives of nipecotic acid and related compounds were tested as inhibitors of γ-aminobutyric acid (GABA) uptake into mini slices. N-Methylnipecotic acid, N,N-dimethyinipecotic acid, N-methylguvacine, and N-methylnicotinic acid were effective inhibitors. None of them, however, were as potent as nipecotic acid itself. All the effective inhibitors, including nipecotic acid, also inhibited the uptake of L-proline, but to a much lesser extent. Four of the test compounds produced a depressant action on cerebral cortical neurons, but even N-methylisoguvacine, the most potent in this respect, was considerably less active than GABA. None of the test compounds caused any clearly discernible changes in the gross behaviour or appearance of mice in the 1-h period following intramuscular injection. It was concluded that methylation of the N atom of nipecotic acid and its derivatives was unlikely to lead to the development of agents with greater experimental or therapeutic potential than that of nipecotic acid itself, if the action of the agent was dependent on its effects on GABA uptake.

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Superoxide Radical-Mediated Alteration of Synaptosome Membrane Structure and High-Affinity ?-[14C]Aminobutyric Acid Uptake

Journal of Neurochemistry ◽

10.1111/j.1471-4159.1986.tb13092.x ◽

1986 ◽

Vol 47 (6) ◽

pp. 1804-1813 ◽

Cited By ~ 15

Author(s):

Edmund A. Debler ◽

Henry Sershen ◽

Abel Lajtha ◽

Joseph F. Gennaro

Keyword(s):

Membrane Structure ◽

Superoxide Radical ◽

Aminobutyric Acid ◽

Acid Uptake ◽

High Affinity ◽

Synaptosome Membrane

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Identification and Characterization of γ-Aminobutyric Acid Uptake System GabPCg(NCgl0464) in Corynebacterium glutamicum

Applied and Environmental Microbiology ◽

10.1128/aem.07406-11 ◽

2012 ◽

Vol 78 (8) ◽

pp. 2596-2601 ◽

Cited By ~ 33

Author(s):

Zhi Zhao ◽

Jiu-Yuan Ding ◽

Wen-hua Ma ◽

Ning-Yi Zhou ◽

Shuang-Jiang Liu

Keyword(s):

Amino Acid ◽

Corynebacterium Glutamicum ◽

Dry Weight ◽

Aminobutyric Acid ◽

Gaba Uptake ◽

Acid Uptake ◽

Uptake System ◽

Content Type ◽

Gaba Transporters ◽

New Type

ABSTRACTCorynebacterium glutamicumis widely used for industrial production of various amino acids and vitamins, and there is growing interest in engineering this bacterium for more commercial bioproducts such as γ-aminobutyric acid (GABA). In this study, aC. glutamicumGABA-specific transporter (GabPCg) encoded byncgl0464was identified and characterized. GabPCgplays a major role in GABA uptake and is essential toC. glutamicumgrowing on GABA. GABA uptake by GabPCgwas weakly competed byl-Asn andl-Gln and stimulated by sodium ion (Na+). TheKmandVmaxvalues were determined to be 41.1 ± 4.5 μM and 36.8 ± 2.6 nmol min−1(mg dry weight [DW])−1, respectively, at pH 6.5 and 34.2 ± 1.1 μM and 67.3 ± 1.0 nmol min−1(mg DW)−1, respectively, at pH 7.5. GabPCghas 29% amino acid sequence identity to a previously and functionally identified aromatic amino acid transporter (TyrP) ofEscherichia colibut low identities to the currently known GABA transporters (17% and 15% toE. coliGabP andBacillus subtilisGabP, respectively). The mutant RES167 Δncgl0464/pGXKZ9 with the GabPCgdeletion showed 12.5% higher productivity of GABA than RES167/pGXKZ9. It is concluded that GabPCgrepresents a new type of GABA transporter and is potentially important for engineering GABA-producingC. glutamicumstrains.

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Inhibition of high-affinity gamma-aminobutyric acid uptake in primary astrocyte cultures by phorbol esters and phospholipase C

Biochemical Journal ◽

10.1042/bj2750435 ◽

1991 ◽

Vol 275 (2) ◽

pp. 435-439 ◽

Cited By ~ 40

Author(s):

J Gomeza ◽

M Casado ◽

C Gimenez ◽

C Aragon

Keyword(s):

Phospholipase C ◽

Glial Cells ◽

Kinase Inhibitor ◽

Primary Cultures ◽

Aminobutyric Acid ◽

Gaba Uptake ◽

Acid Uptake ◽

Gamma Aminobutyric Acid ◽

Gaba Transport ◽

High Affinity

The effects of phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C (PKC), on high-affinity Na(+)-dependent gamma-aminobutyric acid (GABA) uptake were investigated in primary cultures of neurons and glial cells from rat brain cortex. Incubation of glial cells with PMA led to concentration- and time-dependent decreases in the GABA transport in glial cells. This effect could be completely suppressed by addition of the PKC inhibitor H7. The PMA effects could be mimicked by oleoylacetylglycerol, the diacylglycerol kinase inhibitor R59022 and exogenous phospholipase C. Treatment with PMA did not affect GABA transport in neuronal cells.

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